{"files"=>["https://ndownloader.figshare.com/files/2086799"], "description"=>"<p>The sites shown in purple are those identified by Koel et al. 2013 [<a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004940#ppat.1004940.ref021\" target=\"_blank\">21</a>] to be critical for antigenic cluster transitions. Only one of these sites has a <i>dN</i>/<i>dS</i> significantly above one, site 145. The sites shown in red are those that our geometrical model predicts to have <i>dN</i>/<i>dS</i> > 1. (Half of those sites have observed <i>dN</i>/<i>dS</i> > 1.) Note that our model predicts only sites on the basal side of sialic acid to be under positive selection, since our reference point for proximity is site 224. Site 145, the only purple site under positive selection, is also the only purple site on the basal side of sialic acid.</p>", "links"=>[], "tags"=>["IEDB epitope sites", "Geometric Constraints Dominate", "Influenza H 3N Hemagglutinin", "epitope sites", "proximity", "2 percentage points", "accessibility", "influenza antigenic sites", "variation", "H 3 epitope sites", "ha", "H 3 hemagglutinin evolution"], "article_id"=>1429522, "categories"=>["Biological Sciences"], "users"=>["Austin G. Meyer", "Claus O. Wilke"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004940.g004", "stats"=>{"downloads"=>0, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Sites_identified_by_Koel_et_al_2013_and_those_predicted_to_have_dN_dS_1_/1429522", "title"=>"Sites identified by Koel et al. 2013 and those predicted to have <i>dN</i>/<i>dS</i> > 1.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-05-28 04:07:53"}

{"files"=>["https://ndownloader.figshare.com/files/2086809", "https://ndownloader.figshare.com/files/2086810", "https://ndownloader.figshare.com/files/2086811", "https://ndownloader.figshare.com/files/2086812"], "description"=>"<div><p>We have carried out a comprehensive analysis of the determinants of human influenza A H3 hemagglutinin evolution. We consider three distinct predictors of evolutionary variation at individual sites: solvent accessibility (as a proxy for protein fold stability and/or conservation), Immune Epitope Database (IEDB) epitope sites (as a proxy for host immune bias), and proximity to the receptor-binding region (as a proxy for one of the functions of hemagglutinin-to bind sialic acid). Individually, these quantities explain approximately 15% of the variation in site-wise <i>dN/dS</i>. In combination, solvent accessibility and proximity explain 32% of the variation in <i>dN/dS</i>; incorporating IEDB epitope sites into the model adds only an additional 2 percentage points. Thus, while solvent accessibility and proximity perform largely as independent predictors of evolutionary variation, they each overlap with the epitope-sites predictor. Furthermore, we find that the historical H3 epitope sites, which date back to the 1980s and 1990s, only partially overlap with the experimental sites from the IEDB, and display similar overlap in predictive power when combined with solvent accessibility and proximity. We also find that sites with <i>dN/dS</i> > 1, i.e., the sites most likely driving seasonal immune escape, are not correctly predicted by either historical or IEDB epitope sites, but only by proximity to the receptor-binding region. In summary, a simple geometric model of HA evolution outperforms a model based on epitope sites. These results suggest that either the available epitope sites do not accurately represent the true influenza antigenic sites or that host immune bias may be less important for influenza evolution than commonly thought.</p></div>", "links"=>[], "tags"=>["IEDB epitope sites", "Geometric Constraints Dominate", "Influenza H 3N Hemagglutinin", "epitope sites", "proximity", "2 percentage points", "accessibility", "influenza antigenic sites", "variation", "H 3 epitope sites", "ha", "H 3 hemagglutinin evolution"], "article_id"=>1429532, "categories"=>["Biological Sciences"], "users"=>["Austin G. Meyer", "Claus O. Wilke"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1004940.s001", "https://dx.doi.org/10.1371/journal.ppat.1004940.s002", "https://dx.doi.org/10.1371/journal.ppat.1004940.s003", "https://dx.doi.org/10.1371/journal.ppat.1004940.s004"], "stats"=>{"downloads"=>2, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Geometric_Constraints_Dominate_the_Antigenic_Evolution_of_Influenza_H3N2_Hemagglutinin_/1429532", "title"=>"Geometric Constraints Dominate the Antigenic Evolution of Influenza H3N2 Hemagglutinin", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-05-28 04:07:53"}